Adhesions, typically brought about by the formation of internal scar tissue, are one of the leading causes of post surgical complications. They are formed as a result of the body's natural response to the trauma of surgery. Body tissue repairs itself naturally following any incision, cauterization, suturing or other means of trauma. Adhesions typically form when two or more surfaces, such as the surfaces of discrete tissues, stick together at the site of surgery during the natural healing process. Adhesions can occur following virtually all types of surgeries and even the most careful and skilled surgeons find it difficult to avoid the formation of adhesions.
For a variety of reasons, adhesions occur in a very high percentage of patients after surgeries such as abdominal and pelvic surgery, and are particularly problematic there. Adhesions present a particular problem at places in the body where a surgeon cuts or handles tissues that normally should remain separate. Such tissues will sometimes become stuck together, causing fibrous scar tissue to form. When this happens, surgical complications result. The most common complications include bowel obstruction, female infertility, and chronic debilitating pain. In addition to pain and bodily complications, adhesions lead to increased medical expenses. Costs include subsequent surgeries to remove or separate adhesions, doctor visits, pain medication and compensation for lost work time. Also, if a patient were to have a subsequent operation in the same surgical site, such operation can be complicated by existing adhesions. Surgeons have to spend a considerable amount of time removing the adhesions before a new procedure can begin. This may also prolong the patient's recovery time and increases the risk and cost of the surgery.
Therefore, prevention of adhesions is an important goal of surgical practice. Many approaches to prevent adhesions have been suggested, but they either have not generally withstood rigorous clinical examination or they have major practical limitations. One such approach is to perform an operation to remove the adhesions. In the United States, several procedures are performed annually to remove adhesions. However, many times these operations are not effective because the adhesions simply reform.
Another approach to preventing adhesions involves the use of agents such as anti-inflammatory agents, non-steroidal anti-inflammatory drugs, anticoagulants, and fibrinolytic agents to reduce the inflammatory response during surgery. Anti-inflammatory agents would be helpful if used in large doses, but since large doses can have negative effects on other organs (immunosuppression and delayed wound healing), the positive benefits of preventing adhesions tend to be outweighed by the other negative effects. Moreover, the reports of their results in reducing adhesions have not been encouraging. See Gere diZerega, MD, “Contemporary Adhesion Prevention”, Center for Endometriosis Care Newsletter, Copyright 1999 (see www.centerforendo.com/news/adhesions/adhesions.htm).
One new advance in the field of adhesion prevention is the development of barriers to be used in surgical procedures. One type of a barrier includes liquid solutions that are placed on the sites of surgery with the aim of separating tissue at risk surfaces. One example of a liquid barrier includes Gliatech's ADCON® products, which are provided in the form of resorbable gels and solutions designed to inhibit adhesions. The ADCON® products are applied directly to the surgical site. The gels and solutions are themselves resorbed by the body within approximately four weeks, and therefore, do not require surgical removal. See the ADCON® products brochure, Gliatech, Inc., 1998. One problem with liquid barriers, however, is that they tend to be absorbed too rapidly, so their duration of action is not sufficient to cover the period during which adhesives are most likely to form.
Another example of a barrier to be used in adhesion prevention is a structural barrier such as a sheet of material, which is introduced between layers of traumatized tissue during surgery. An ideal structural barrier preferably persists during the first critical stages of healing, has no effect on wound healing, is bioresorbable, and does not promote bacterial growth.
One well-known structural barrier product that has been developed to prevent adhesion formation is provided under the tradename Seprafilm™, manufactured by Genzyme Corporation. Seprafilm™ products are transparent films that are designed to act as a temporary barrier between two tissue layers during the early days of wound healing, thereby reducing adhesion formation. More specifically, Seprafilm™ products are sterile bioresorbable transparent adhesion barriers composed of two anionic polysaccharides, namely sodium hyaluronate and carboxymethylcellulose. Together, these two biopolymers are chemically modified with an activating agent 1-(3-dimethylaminopropyl)-3-ethylcarbodimide hydrochloride. Seprafilm™ products hydrate to a gel within 24–48 hours following placement in the body and then slowly resorb from the abdominal cavity in about five days. They are excreted from the body within 28 days. See the Seprafilm™ products brochure, Genzyme Corporation, 2000.
When used, Seprafilm™ products are placed at a desired site within the body, with that desired site being as dry as possible. Before placing Seprafilm™ products in the body, the site of application is thoroughly aspirated of excess fluid. The Seprafilm™ products are kept in their package until immediately before use. In one form, for example, the film measures 5 inches by 6 inches, though it can also be cut with scissors to achieve a desired size and shape. When applying, the surgeon avoids contact with any tissue surfaces until directly at the site of application. If contact does occur, moderate application of standard irrigation solution is used to gently dislodge the film from the unintended tissue surface. Once at the proper site of application, the biomaterial is adhered to the tissue by gently pressing the biomaterial down with a dry glove or instrument. The biomaterial remains at the site of application until it dissolves into a gel. See the Seprafilm™ products brochure, Genzyme Corporation, 2000.
While Seprafilm™ products and others have provided several advantages in this field, they still suffer several drawbacks. The primary drawback is that, while they do reduce the occurrence of adhesions, the amount reduced is less than ideal. For example, Genzyme reports that clinical findings have shown that when used in abdominal procedures, Seprafilm™ products have prevented adhesions in 51% of patients, and that only 15% of patients treated with Seprafilm™ products had dense adhesions. While the prevention of adhesions by 51% is helpful, it is still less than ideal. Hence, there remains a need for an improved composition and method for reducing surgical adhesions, and particularly compositions that will provide an optimal combination of ease of use, adhesion reduction, and applicability to a variety of surgical situations. The present invention addresses this need.